ABSTRACT
The cerebral ischemia-reperfusion injury (CIRI) after the cardiac arrest (CA)-cardiopulmonary resuscitation (CPR) was a complex pathophysiology process. Nitric oxide (NO) is a small molecule that mediates cell signal transduction in vivo and plays an important role in the regulation of brain function during ischemia/reperfusion (I/R). S-nitrosoglutathione reductase (GSNOR) inhibitor can regulate the synthesis and release of NO in vivo and has a protective effect on CIRI. Therefore, early administration of GSNOR to CA-CPR patients could be the main treatment method to improve the prognosis of those patients. A large number of studies have been done to improve the prognosis of CA-CPR in recent years. In order to provide reference for further research on the treatment and brain protection of CIRI after CA-CPR, the article reviewed the main mechanisms of brain injury after CA-CPR, the protective effect and mechanism of NO on cerebral I/R injury, the production and regulation of NO, in vivo, and the protective effect of GSNOR inhibitors on CIRI, especially the research progress of GSNOR inhibitors.
ABSTRACT
Objective To investigate the effect of S-Nitrosoglutathione (GSNO)on acute ischemia reperfusion (I/R)induced in-testinal barrier function lesion in a mouse model.Methods Twenty-four 6-8-year-old C57BL/6 mice were divided into 3 groups,8 for each:(1)the sham group;(2)the I/R group;(3)the I/R+GSNO group.The mouse intestine I/R model was established by the occlusion of the superior mesenteric artery temporarily followed by reperfusion for 6 h.Histological changes in the small intestine were observed after HE staining;the expression of claudin-1 protein in the intestine epithelium was assessed by immunohistochem-istry staining as well as western blot analysis.Results Both HE staining and immunohistochemistry results showed the integrate intestinal villi with the continuous Claudin-1 expression alone the villi in the sham group;the intestinal villi of the I/R group partial-ly detached,thickened,crooked and fractured,with the obvious disconnection of Claudin-1 staining alone the top of the villi;while the intestinal villi of the I/R+GSNO group were neatly arranged and damage to intestinal mucosa was much alleviated,accompanied with the marked restoration of the continuity of claudin-1 staining.Compared to the sham group,claudin-1 protein level of for the I/R group and the I/R+GSNO group decreased by 32.5% and 13.8% respectively (P <0.05);and compared to the I/R group,clau-din-1 protein level of the I/R+GSNO group increased by 27.8% (P <0.05).Conclusion Protein level of claudin-1 would decrea-ses after I/R,and pretreatment with GSNO can effectively relieve the damage of intestinal mucosal structure as well as intestinal tight junction barrier through upregulating the expression of claudin-1 protein.
ABSTRACT
OBJECTIVE: To investigate the role of ginsenoside Rg1 effect on S-nitrosoglutathione (GSNO) induced human endothelial cells injury, and to further find the potential mechanisms of Rg1 effects.
ABSTRACT
PURPOSE: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. METHODS: Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. RESULTS: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. CONCLUSION: Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.
OBJETIVO: Avaliar a toxidade na superfície ocular de dois compostos doadores de óxido nítrico em modelos ex vivo e in vivo: S-nitrosoglutationa (GSNO) e S-nitroso-N-acetilcisteína (SNAC), em uma matriz de hidroxipropil metilcelulose (HPMC) nas concentrações finais de 1,0 and 10,0 mM. MÉTODOS: As toxicidades de GSNO e SNAC foram avaliadas clinicamente e histologicamente em modelo ex vivo usando globos oculares porcinos recém excisados. Experimentos in vivo foram realizados com 20 coelhos albinos que foram randomizados em 4 grupos (5 animais em cada): Os grupos 1 e 2 receberam instilações de 150 µL de solução aquosa de HPMC contendo GSNO 1,0 e 10,0 mM, respectivamente, em um dos olhos; Os grupos 3 e 4 receberam instilações de 150 µL de solução aquosa de HPMC contendo SNAC 1,0 and 10,0 mM, respectivamente, em um dos olhos. Os olhos contralaterias em cada grupo receberam solução aquosa de HPMC como controle. Todos os animais foram clinicamente avaliados em lâmpada de fenda e os olhos foram pontuados de acordo com o teste de Draize modificado e analisados histologicamente. RESULTADOS: Os globos oculares porcinos não apresentaram sinais de perfuração, erosão, opacidade da córnea ou outros danos graves. Esses resultados foram confirmados pela análise histológica. Não houve diferença entre os olhos dos coelhos tratados e controles de acordo com a pontuação do teste de Draize em todos os grupos (p>0,05). Todas as formulações apresentaram um escore médio menor do que 1 e foram classificadas como "não-irritantes". Não houve evidência de toxicidade tecidual nas análises histológicas em todos os animais. CONCLUSÃO: Soluções aquosas de HPMC contendo GSNO e SNAC em concentrações até 10,0 mM não induzem irritação ocular.
Subject(s)
Animals , Male , Rabbits , Acetylcysteine/analogs & derivatives , Eye/drug effects , Nitric Oxide Donors/toxicity , S-Nitrosoglutathione/toxicity , Acetylcysteine/administration & dosage , Acetylcysteine/toxicity , Dose-Response Relationship, Drug , Eye/pathology , Instillation, Drug , Nitric Oxide Donors/administration & dosage , Random Allocation , S-Nitrosoglutathione/administration & dosage , SwineABSTRACT
Objective To clarify the effect of NO on hypoxic myocardium in rats.Methods Myocardial cells from neonatal Wistar rats aged 1-2 days cultured for 4-6 days,then pretreated with GSNO(30,200,4 000 ?mol/L)were exposed to normoxia(N)or hypoxia(H)(1%O2,5%CO2 and 94%N2)for 4 h.The NO content and LDH in the supernatant were detected.Results NO of 1.43,7.2 and 70 ?mol/L were detected respectively in the supernatant of hypoxic myocardial cells treated by GSNO(30,200 and 4 000 ?mol/L).Compared with normoxic group,LDH activity increased and myocardial cell activity decreased markedly in H+G30 and H+G4000 groups but less injury was observed in H+G200 group.Conclusion NO of certain concentration can markedly abate myocardial cell injury induced by hypoxia.